Expression of the liver Na+-independent organic anion transporting polypeptide (oatp-1) in rats with bile duct ligation.
OBJECTIVE
In rats with cholestasis due to bile duct ligation, the expression of the Na+-dependent taurocholate co-transporting polypeptide, the major uptake system for conjugated bile acids in hepatocytes, is down-regulated. Our purpose was to examine the expression of the organic anion transporting polypeptide, a Na+-independent uptake system for bile acids and organic anions, in rats with bile duct ligation, and to compare the expression of organic anion transporting polypeptide to that of Na+-dependent taurocholate co-transporting polypeptide.


METHODS
Rats with bile duct ligation were studied after 1, 3 or 7 days. The expression of organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide proteins was examined by Western blot analysis and steady-state mRNA levels were determined by Northern blot analysis using cDNAs encoding organic anion transporting polypeptide and Na+-dependent taurocholate co-transporting polypeptide. Sham-operated animals were used as controls.


RESULTS
The expression of organic anion transporting polypeptide protein was slightly, but not significantly, decreased 1 day after ligation (10.3%); it was markedly decreased after 3 days (56.9%; p<0.03) and 7 days (46.8%; p<0.05) compared to sham-operated animals. Steady-state mRNA levels of organic anion transporting polypeptide were decreased by 79.7% (p<0.04), 48.8% (p<0.02) and 57.4% (p<0.02) after 1, 3 and 7 days respectively. For comparison, Na+-dependent taurocholate co-transporting polypeptide protein and mRNA levels were decreased by 73.8% (p<0.03) and 70.0% (p<0.05) at 1 day and remained low after 3 and 7 days.


CONCLUSIONS
In rats with bile duct ligation, the expression of organic anion transporting polypeptide protein and mRNA is down-regulated. Down-regulation of organic anion transporting polypeptide seems less pronounced than that of Na+-dependent taurocholate co-transporting polypeptide. Nevertheless, it could contribute to a decreased uptake of potentially toxic bile acids or organic anions in this situation.
Dumont
M
M
Unité de Recherches de Physiopathologie Hépatique (INSERM U24), Hôpital Beaujon, Clichy, France.
Jacquemin
E
E
D'Hont
C
C
Descout
C
C
Cresteil
D
D
Haouzi
D
D
Desrochers
M
M
Stieger
B
B
Hadchouel
M
M
Erlinger
S
S
D000818:Animals; D027321:Anion Transport Proteins; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000032:analysis* / Q000235:genetics; D002779:Cholestasis / Q000378:metabolism*; D008099:Liver / Q000737:chemistry*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*
D027321:Anion Transport Proteins; D002352:Carrier Proteins; D012964:Sodium